Research group Kristina Broliden

The Broliden group works within the field of human mucosal immunology and is divided into three teams: Kristina Broliden (HIV) Annelie Tjernlund (HIV) and Lars Öhrmalm (infections in immunosuppressed patients). The research group is located at Bioclinicum, Department of Medicine Solna, Karolinska Institutet and the Department of Infectious Diseases, Karolinska University Hospital.

Kristina Broliden

Professor/senior physician
K Broliden
K2 Department of Medicine, Solna

Kristina Broliden, Professor, Group Leader
Current position
Professor and Senior Consultant, Division of Infectious Diseases, Karolinska Institutet and Department of Infectious Diseases, Karolinska University Hospital
Department of Medicine Solna, Karolinska Institutet

Adress

Karolinska Institutet
Institutionen för medicin, Solna
Avdelningen för infektionssjukdomar
Visionsgatan 4, J7:20
171 64 Solna

Kristina Broliden Group

Photo: Stefan Zimmerman

Team Kristina Broliden

Kristina Broliden,Professor, MD, Group Leader

Fariba Foroogh, MD, Labaratory manager

Frideborg Bradley, Postdoc, Affiliated

Adam Burgener, Professor, Affiliated

Gabriella Edfeldt, Postdoc

Thomas Hägglöf, Postdoc

Vilde Kaldhusdal, PhD student

Alexandra Åhlberg, MD, PhD student

Nora Benhach, Visiting student

GENITAL MUCOSAL BARRIERS AGAINST HIV-INFECTION

Environmental factors including endogenous microbiome, hormonal contraceptive use and sexually transmitted, genital infections affect the susceptibility to HIV infection as demonstrated in epidemiological and experimental studies. The molecular mechanisms behind these findings are however poorly defined. Our group aims to study how the human female genital tract is affected by these factors by assessing tissue samples and cervicovaginal secretions from large cohorts of Swedish and Kenyan women who are sexually exposed to HIV infection. Genital samples are defined by expression of epithelial junction proteins, distribution and density of HIV receptors and innate immune proteins by using in situ imaging analysis, tissue explants models as well as protein and transcriptimal profiling. By exploring some of the underlying mechanisms for a dysfunctional mucosal barrier we hope to contribute to the development of topical prophylactic compounds and to the prescription of optimal contraceptive methods to women.

The aim of the Broliden/Tjernlund teams is to characterize genital mucosal barriers against HIV-infection.

The aim of the Lars Öhrmalm team is to characterize infections in immunosuppressed patients to improve antiviral and antibiotic treatment.

Team Annelie Tjernlund

 

Team Lars Öhrmalm

INFECTIONS IN IMMUNOSUPPRESSED PATIENTS

Infections in patients with haematological disorders

Early diagnosis of severe virus infections in immunosuppressed patients has undergone major advances during recent years. Modern molecular techniques have resulted in reduction of morbidity and mortality associated with these infections. Through experimental and clinical studies on human parvovirus B19 infections, we have shown that this common infection can also result in severe morbidity and lethal complications. The clinical course and corresponding immune responses are defined in various patient categories. Clinical protocols and therapeutic interventions have been launched as a result of these studies. The clinical and scientific focus of these studies has also been broadened to include other respiratory tract infections in children and adults. We have here contributed to the knowledge of how to diagnose and initiate early treatment in these cases and which pathogens can be defined as etiological agents of the symptoms. Definition of etiological causes for severe complications in patients can result in better antiviral treatment options and development of not only antiviral compounds but also combination treatments including modern immunomodulatory drugs.

Infections during pregnancy

Parvovirus B19 is a pathogen that can cause severe and lethal fetal infections if the mother is infected during pregnancy. Together with our colleagues in gynecology and pathology we have developed better diagnostic tools and treatment options for these cases. We have also co-founded a national reference center that allows consultancies in urgent and complicated cases of both bacterial and viral infections during pregnancy. The overall information is available for both the public and health professionals in a widely spread and frequently used database that is up-dated monthly with new clinical and scientific information (www.infpreg.se).

Infections in patients with respiratory tract diseases

Despite the use of established viral PCR methods, approximately 30% of all presumed viral respiratory tract infections are not detected with current methods. We have studied respiratory tract infections and how co-infections of virus and bacterial agents interact with the host immune response in the airway mucosa. For these studies our group has included healthy children with acute onset of severe respiratory tract infections, children suffering from asthmatic disorders and healthy control children. The project now aims to improve diagnostics to distinguish viral from bacterial pneumonia and optimize treatment in patients with severe infections. Mass spectrometry-based proteomic analyses are used as a tool to assess host-microbe interaction in respiratory tract infections. Identifying mucosal biomarkers may provide a rapid, accurate and clinically useful test for early identification of patients with severe viral pneumonia. This is now explored in a number of ongoing clinical studies initiated by us as a result of our clinical activities.

Selected publications

Regular use of depot medroxyprogesterone acetate causes thinning of the superficial lining and apical distribution of HIV target cells in the human ectocervix.
Edfeldt G, Lajoie J, Röhl M, Oyugi J, Åhlberg A, Khalilzadeh-Binicy B, et al
J. Infect. Dis. 2020 Aug;():

The Feasibility of Host Transcriptome Profiling as a Diagnostic Tool for Microbial Etiology in Childhood Cancer Patients with Febrile Neutropenia.
Wahlund M, Sinha I, Broliden K, Saghafian-Hedengren S, Nilsson A, Berggren A
Int J Mol Sci 2020 Jul;21(15):

The neovaginal microbiome of transgender women post-gender reassignment surgery.
Birse KD, Kratzer K, Zuend CF, Mutch S, Noël-Romas L, Lamont A, et al
Microbiome 2020 05;8(1):61

Impact of Q-Griffithsin anti-HIV microbicide gel in non-human primates: In situ analyses of epithelial and immune cell markers in rectal mucosa.
Günaydın G, Edfeldt G, Garber DA, Asghar M, Noȅl-Romas L, Burgener A, et al
Sci Rep 2019 12;9(1):18120

The Role of TPMT, ITPA, and NUDT15 Variants during Mercaptopurine Treatment of Swedish Pediatric Patients with Acute Lymphoblastic Leukemia.
Wahlund M, Nilsson A, Kahlin AZ, Broliden K, Myrberg IH, Appell ML, et al
J. Pediatr. 2020 01;216():150-157.e1

Increased Cervical CD4+CCR5+ T Cells Among Kenyan Sex Working Women Using Depot Medroxyprogesterone Acetate.
Lajoie J, Tjernlund A, Omollo K, Edfeldt G, Röhl M, Boily-Larouche G, et al
AIDS Res. Hum. Retroviruses 2019 03;35(3):236-246

A High-throughput Bead-based Affinity Assay Enables Analysis of Genital Protein Signatures in Women At Risk of HIV Infection.
Månberg A, Bradley F, Qundos U, Guthrie BL, Birse K, Noël-Romas L, et al
Mol. Cell Proteomics 2019 03;18(3):461-476

The CD4-CD8- MAIT cell subpopulation is a functionally distinct subset developmentally related to the main CD8+ MAIT cell pool.
Dias J, Boulouis C, Gorin JB, van den Biggelaar RHGA, Lal KG, Gibbs A, et al
Proc. Natl. Acad. Sci. U.S.A. 2018 12;115(49):E11513-E11522

Ex Vivo Infection of Human Lymphoid Tissue and Female Genital Mucosa with Human Immunodeficiency Virus 1 and Histoculture.
Introini A, Vanpouille C, Fitzgerald W, Broliden K, Margolis L
J Vis Exp 2018 10;(140):

The vaginal microbiome amplifies sex hormone-associated cyclic changes in cervicovaginal inflammation and epithelial barrier disruption.
Bradley F, Birse K, Hasselrot K, Noël-Romas L, Introini A, Wefer H, et al
Am. J. Reprod. Immunol. 2018 07;80(1):e12863

Human Immunodeficiency Virus-Infected Women Have High Numbers of CD103-CD8+ T Cells Residing Close to the Basal Membrane of the Ectocervical Epithelium.
Gibbs A, Buggert M, Edfeldt G, Ranefall P, Introini A, Cheuk S, et al
J. Infect. Dis. 2018 07;218(3):453-465

MAIT cells reside in the female genital mucosa and are biased towards IL-17 and IL-22 production in response to bacterial stimulation.
Gibbs A, Leeansyah E, Introini A, Paquin-Proulx D, Hasselrot K, Andersson E, et al
Mucosal Immunol 2017 01;10(1):35-45

Seminal plasma induces inflammation and enhances HIV-1 replication in human cervical tissue explants.
Introini A, Boström S, Bradley F, Gibbs A, Glaessgen A, Tjernlund A, et al
PLoS Pathog. 2017 May;13(5):e1006402

MAIT cells reside in the female genital mucosa and are biased towards IL-17 and IL-22 production in response to bacterial stimulation.
Gibbs A, Leeansyah E, Introini A, Paquin-Proulx D, Hasselrot K, Andersson E, et al
Mucosal Immunol 2017 01;10(1):35-45

Genital Injury Signatures and Microbiome Alterations Associated With Depot Medroxyprogesterone Acetate Usage and Intravaginal Drying Practices.
Birse KD, Romas LM, Guthrie BL, Nilsson P, Bosire R, Kiarie J, et al
J. Infect. Dis. 2017 02;215(4):590-598